Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium

Abstract

Lead (Pb 2+ ) poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g) before and after the addition of increasing concentrations of lead acetate (3,7,10,30, 70, 100, and 300 µM) to the bath. Changes in rate of stimulation (0.1-1.5 Hz), relative potentiation after pauses of 15, 30, and 60 s, effect of Ca 2+ concentration (0.62, 1.25, and 2.5 mM), and the effect of isoproterenol (20 ng/mL) were determined before and after the addition of 100 µM Pb 2+ . Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz) and measuring the activity of the myosin ATPase. Pb 2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 µM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 µM Pb 2+ treatment. Extracellular Ca 2+ increment and isoproterenol administration increased force development but after 100 µM Pb 2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca 2+ influx. Concentration of 100 µM Pb 2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb 2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle.

Acute lead-induced vasoconstriction in the vascular beds of isolated perfused rat tails is endothelium-dependent

“…To ensure that the effects were not dependent on time, another group of rats was used under the same conditions in a time control experiment performed 1 h later, after iv administration of 0.9% saline. This lead concentration was selected because it is known to produce a clear negative inotropic effect and to reduce myosin ATPase activity in the rat myocardium (23).…”

Acute exposure to lead increases myocardial contractility independent of hypertension development

“…However, other reports have indicated that acute lead administration (30 µM in the bath) to perfused rat hearts attenuates positive inotropic responses 15. In rat papillary muscles, acute 100 µM lead in the bath, although not affecting sarcoplasmic reticulum activity, has a negative inotropic effect and reduces myosin ATPase activity 17. Lead action contributing to calcium channel blocking has also been reported in rat myocytes and Xenopus laevis oocytes 16.…”

“…The first contraction after rest was taken as an index of sarcolemmal calcium influx 18. Taking into account that the rat myocardium saturates its positive inotropic response at extracellular Ca 2+ concentrations lower than those for other species 17, the protocols using isoproterenol were performed with reduced extracellular Ca 2+ concentrations (0.62 mM). In the last protocol, tetanic tension was elicited before (control condition - time 0) and at 15, 30, 45, 60, and 90 min after lead administration by high frequency stimulation (10 Hz for 15 s).…”

“…In agreement with those findings, Bernal et al 16, using 1 to 30 µM lead, also reported calcium channel blocker action in rat myocytes and Xenopus laevis oocytes. In papillary muscles, acute 100 µM lead added to the bath had a negative inotropic effect 17, suggesting that lead affects heart function. However, it is necessary to emphasize that low lead concentrations (24.2 ± 1.8 µg/dL) cause positive inotropism 14, while negative inotropism has been associated with higher lead concentrations (100 µM) 17.…”

Low-level Chronic Lead Exposure Impairs Neural Control of Blood Pressure and Heart Rate in Rats

“…*P \ 0.05 when compared to the same parameter versus control group. All comparisons were performed using an unpaired Student's t test isolated rat cardiac muscles exposed to 8 lM lead acetate exhibited increased contractility [64], but 30-100 lM lead decreased force by reducing calcium influx and myosin ATPase activity [65]. Nevertheless, by using a chronic model of lead exposure in the rat, Fioresi et al [3] demonstrated that despite no change in the contractile force of isolated cardiac muscle, there was strong evidence of impaired sarcoplasmic reticulum (SR) function.…”